Synthesis Study On Azithromycin

Azithromycin is a new antibiotic produced on the basis of the modification of erythromycin structure.Azithromycin could be applied to the respiratory diseases caused by the spread of susceptible bacteria,skin and soft tissue infections and chlamydia-induced transmission diseases in clinical.Azithromycin was more popular in clinical than erythromycin due to that azithromycin had more broader antibacterial spectrum and more comprehensive pharmacology.In this paper,on the basis of comprehensive synthesis of azithromycin reported in the literature and the workshop process,the synthesis process of azithromycin,key process parameters and catalyst revival process of hydrogenation reduction were optimized.and a pilot scale-up validation and workshop scale production was performed.The best process and reaction conditions had been determined.The main research findings were as follows:Firstly,erythromycin-6,9-iminoether was prepared from erythromycin thiocyanate by sulfonation and rearrangement reaction in a one-pot process.Therefore the yield of erythromycin-6,9-iminoether was increased from 54.0 % to 74.1 %.Secondly,some key parameters of deuteration,rearrangement,reduction and methylation reactions were optimized.Then the optimized process parameters for the synthesis of azithromycin were determined.The finally obtaind content of erythromycin-6,9-iminoether was increased from 90.5 % to 93.1 % and the content of azithromycin was increased from 96.4 % to 97.7 %Thirdly,in the deuteration reaction,sodium carbonate was used instead of triethylamine as the acid-binding agent,which could solve the problem that triethylamine and methanol were not easily solely recovered and the annual save the raw material cost about 1.2 million yuan for the enterprise.In the methylation reaction,acetone was used instead of chloroform in the original process as the reaction solvent,which reduced the step of distilling off and recovering chloroform,avoided the use of chloroform,reduced the cost of raw materials and reduced pollution to the environment.Furthmore,a new Pt/C catalyst revival treatment process was developed,which could solve the problem of the yield and quality instability of dihydroerythromycin caused by deactivation of the catalyst in the hydrogenation reduction reaction,so that the yield of dihydroerythromycin over 88.0 % and the content over 95.0 %.Finally,the optimized process has achieved good results through the large-scale application of the workshop.The production cost of the raw material of the unit is reduced by 326 yuan /kg.Since the new process has been applied to the workshop,the cumulative production of azithromycin is 61.2 tons,and the cost of the production of raw materials is 19 million 951.2 thousand yuan for the enterprise.